scholarly journals The Mammalian Metaorganism: A Holistic View on How Microbes of All Kingdoms and Niches Shape Local and Systemic Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Solveig Runge ◽  
Stephan Patrick Rosshart
Keyword(s):  
Current Knowledge ◽  
Biologically Active ◽  
Comprehensive Overview ◽  
Holistic View ◽  
Systemic Immunity ◽  
Major Interest ◽  
Microbiome Research ◽  
Epithelial Barriers ◽  
And Function ◽  
The Impact

The field of microbiome research has developed rapidly over the past decades and has become a topic of major interest to basic, preclinical, and clinical research, the pharmaceutical industry as well as the general public. The microbiome is a complex and diverse ecosystem and defined as the collection of all host-associated microorganisms and their genes. It is acquired through vertical transmission and environmental exposure and includes microbes of all kingdoms: bacteria, archaea, prokaryotic and eukaryotic viruses, fungi, protozoa, and the meiofauna. These microorganisms co-evolved with their respective hosts over millions of years, thereby establishing a mutually beneficial, symbiotic relationship on all epithelial barriers. Thus, the microbiome plays a pivotal role in virtually every aspect of mammalian physiology, particularly in the development, homeostasis, and function of the immune system. Consequently, the combination of the host genome and the microbial genome, together referred to as the metagenome, largely drives the mammalian phenotype. So far, the majority of studies have unilaterally focused on the gastrointestinal bacterial microbiota. However, recent work illustrating the impact of viruses, fungi, and protozoa on host immunity urges us towards a holistic view of the mammalian microbiome and the appreciation for its non-bacterial kingdoms. In addition, the importance of microbiota on epithelial barriers other than the gut as well as their systemic effects via microbially-derived biologically active compounds is increasingly recognized. Here, we want to provide a brief but comprehensive overview of the most important findings and the current knowledge on how microbes of all kingdoms and microbial niches shape local and systemic immunity in health and disease.

scholarly journals Insights into the Cellular and Molecular Mechanisms That Govern the Fracture-Healing Process: A Narrative Review

2021 ◽  
Vol 10 (16) ◽  
pp. 3554
Author(s):  
Dionysios J. Papachristou ◽  
Stavros Georgopoulos ◽  
Peter V. Giannoudis ◽  
Elias Panagiotopoulos
Keyword(s):  
Fracture Healing ◽  
Bone Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Healing Process ◽  
Bone Architecture ◽  
Multi Stage ◽  
Stage Process ◽  
And Function ◽  
The Impact

Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects.

scholarly journals The Impact of Environmental Chemicals on the Gut Microbiome

2020 ◽  
Vol 176 (2) ◽  
pp. 253-284 ◽  
Author(s):  
Karen Chiu ◽  
Genoa Warner ◽  
Romana A Nowak ◽  
Jodi A Flaws ◽  
Wenyan Mei
Keyword(s):  
Gut Microbiome ◽  
Current Knowledge ◽  
Environmental Chemicals ◽  
Microbial Composition ◽  
Multiple Factors ◽  
Microbiome Research ◽  
Health Related ◽  
Exogenous Factors ◽  
The Impact ◽  
Insight Into

Abstract Since the surge of microbiome research in the last decade, many studies have provided insight into the causes and consequences of changes in the gut microbiota. Among the multiple factors involved in regulating the microbiome, exogenous factors such as diet and environmental chemicals have been shown to alter the gut microbiome significantly. Although diet substantially contributes to changes in the gut microbiome, environmental chemicals are major contaminants in our food and are often overlooked. Herein, we summarize the current knowledge on major classes of environmental chemicals (bisphenols, phthalates, persistent organic pollutants, heavy metals, and pesticides) and their impact on the gut microbiome, which includes alterations in microbial composition, gene expression, function, and health effects in the host. We then discuss health-related implications of gut microbial changes, which include changes in metabolism, immunity, and neurological function.

scholarly journals Microglia: Agents of the CNS Pro-Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1717 ◽  
Author(s):  
José A. Rodríguez-Gómez ◽  
Edel Kavanagh ◽  
Pinelopi Engskog-Vlachos ◽  
Mikael K.R. Engskog ◽  
Antonio J. Herrera ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Reactive Microglia ◽  
Holistic View ◽  
Human Microglia ◽  
Positron Emission ◽  
New Research ◽  
The Impact

The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though the research of microglia spans over a century, the last two decades have increased our understanding exponentially. Here, we discuss the phenotypic transformation from homeostatic microglia towards reactive microglia, initiated by specific ligand binding to pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering receptors expressed on myeloid cells-2 (TREM2), as well as pro-inflammatory signaling pathways triggered such as the caspase-mediated immune response. Additionally, new research disciplines such as epigenetics and immunometabolism have provided us with a more holistic view of how changes in DNA methylation, microRNAs, and the metabolome may influence the pro-inflammatory response. This review aimed to discuss our current knowledge of pro-inflammatory microglia from different angles, including recent research highlights such as the role of exosomes in spreading neuroinflammation and emerging techniques in microglia research including positron emission tomography (PET) scanning and the use of human microglia generated from induced pluripotent stem cells (iPSCs). Finally, we also discuss current thoughts on the impact of pro-inflammatory microglia in neurodegenerative diseases.

The Oxford Handbook of Hope

2017 ◽  
Keyword(s):  
Current Knowledge ◽  
Physical And Mental Health ◽  
Comprehensive Overview ◽  
Future Directions ◽  
Theoretical Perspectives ◽  
The Many ◽  
The Impact ◽  
Made In

The Oxford Handbook of Hope provides a comprehensive overview of current knowledge regarding the science and practice of hope. Hope has long been a topic of interest to philosophers and the general public, but it was only in recent decades that hope became a focus of psychological science. Rick Snyder defined hope as a cognitive trait that helps individuals to identify and pursue goals and consists of two components: pathways, the perceived capacity to identify strategies necessary to achieve goals, and agency, the willpower or motivation to pursue those pathways to achieve goals. Hope has become one of most robust and promising topics in the burgeoning field of positive psychology. This book reviews the progress that has been made in the past 25 years regarding the origins and influence of hope. Topics covered include current theoretical perspectives on how best to define hope and how it is distinct from related constructs, current best practices for measuring and quantifying hope, interventions and strategies for promoting hope across different settings and the lifespan, the impact that hope has on many dimensions and domains of physical and mental health, and the many ways and contexts in which hope promotes resilience and positive functioning. Experts in the field both review what is currently known about the role of hope in different domains and identify topics and questions that can help to guide the next decade of research. The handbook concludes with a collaborative vision on the future directions of the science of hope.

Structural diversity in echinocandin biosynthesis: the impact of oxidation steps and approaches toward an evolutionary explanation

2017 ◽  
Vol 72 (1-2) ◽  
pp. 1-20 ◽  
Author(s):  
Wolfgang Hüttel
Keyword(s):  
Secondary Metabolism ◽  
Current Knowledge ◽  
Structural Diversity ◽  
Special Focus ◽  
Oxidation Reactions ◽  
Metabolic Diversity ◽  
Comprehensive Overview ◽  
Single Organism ◽  
The Impact ◽  
Best Fit

AbstractEchinocandins are an important group of cyclic non-ribosomal peptides with strong antifungal activity produced by filamentous fungi from Aspergillaceae and Leotiomycetes. Their structure is characterized by numerous hydroxylated non-proteinogenic amino acids. Biosynthetic clusters discovered in the last years contain up to six oxygenases, all of which are involved in amino acid modifications. Especially, variations in the oxidation pattern induced by these enzymes account for a remarkable structural diversity among the echinocandins. This review provides an overview of the current knowledge of echinocandin biosynthesis with a special focus on diversity-inducing oxidation steps. The emergence of metabolic diversity is further discussed on the basis of a comprehensive overview of the structurally characterized echinocandins, their producer strains and biosynthetic clusters. For the pneumocandins, echinocandins produced byGlarea lozoyensis, the formation of metabolic diversity in a single organism is analyzed. It is compared to two common models for the evolution of secondary metabolism: the ‘target-based’ approach and the ‘diversity-based’ model. Whereas the early phase of pneumocandin biosynthesis supports the target-based model, the diversity-inducing late steps and most oxidation reactions best fit the diversity-based approach. Moreover, two types of diversity-inducing steps can be distinguished. Although incomplete hydroxylation is a common phenomenon in echinocandin production and secondary metabolite biosynthesis in general, the incorporation of diverse hydroxyprolines at position 6 is apparently a unique feature of pneumocandin biosynthesis, which stands in stark contrast to the strict selectivity found in echinocandin biosynthesis by Aspergillaceae. The example of echinocandin biosynthesis shows that the existing models for the evolution of secondary metabolism can be well applied to parts of the pathway; however, thus far, there is no comprehensive theory that could explain the entire biosynthesis.

scholarly journals Minimal Variation of Human Oral Virome and Microbiome in IgA Deficiency Challenges an Irreplaceable IgA Role for Shaping Oral Commensal Microbiota

2021 ◽  
Author(s):  
de la Cruz Peña Maria José ◽  
Luis Ignacio Gonzalez-Granado ◽  
Inmaculada Garcia-Heredia ◽  
Lucia Maestre Carballa ◽  
Manuel Martinez-Garcia
Keyword(s):  
Immunoglobulin A ◽  
Iga Deficiency ◽  
Control Group ◽  
P Value ◽  
Bacterial Cells ◽  
Holistic View ◽  
Selective Iga Deficiency ◽  
Commensal Microbiota ◽  
And Function ◽  
The Impact

Abstract Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from pathogens. Recently, IgA has been shown to be involved in gut homeostatic regulation by `recognizing´and shaping our commensal microbes. Paradoxically, yet selective IgA-deficiency is often described as asymptomatic and there is a paucity of studies only focused on the mice and human gut microbiome context fully ignoring other niches of our body and our commensal viruses. Here, we used as a model the human oral cavity and employed a holistic view and studied the impact of IgA deficiency on both the human virome and microbiome. Unexpectedly, metagenomic and experimental data in human IgA deficiency indicate minimal-moderate changes in microbiome and virome composition compared to healthy control group and point out to a rather functional, resilient oral commensal viruses and microbes. However, a significant depletion (2-fold) of bacterial cells (p-value < 0.01) and viruses was observed in IgA-deficiency. Our results challenge the view of an irreplaceable IgA role for regulating the composition and function of our commensal microbiota and pose the question whether other “back-up” Ig-independent mechanisms might exist for maintaining a functional commensal microbiome.

scholarly journals Impact of Housing Environment on the Immune System in Chickens: A Review

Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1138 ◽  
Author(s):  
Tanja Hofmann ◽  
Sonja S. Schmucker ◽  
Werner Bessei ◽  
Michael Grashorn ◽  
Volker Stefanski
Keyword(s):  
Immune System ◽  
Allostatic Load ◽  
Current Knowledge ◽  
Future Research ◽  
Poultry Production ◽  
Negative Consequences ◽  
Comprehensive Overview ◽  
Housing Environment ◽  
Wide Range ◽  
The Impact

During their lifespan, chickens are confronted with a wide range of acute and chronic stressors in their housing environment that may threaten their welfare and health by modulating the immune system. Especially chronic stressful conditions can exceed the individual’s allostatic load, with negative consequences for immunity. A fully functional immune system is mandatory for health and welfare and, consequently, also for high productivity and safe animal products. This review provides a comprehensive overview of the impact of housing form, light regime as well as aerial ammonia and hydrogen sulfide concentrations on the immune system in chickens. Certain housing conditions are clearly associated with immunological alterations which potentially impair the success of vaccinations or affect disease susceptibility. Such poor conditions counteract sustainable poultry production. This review also outlines current knowledge gaps and provides recommendations for future research.

scholarly journals The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives

2020 ◽  
Author(s):  
Christophe d'Enfert ◽  
Ann-Kristin Kaune ◽  
Leovigildo-Rey Alaban ◽  
Sayoni Chakraborty ◽  
Nathaniel Cole ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Current Knowledge ◽  
Fungal Host ◽  
Susceptibility To Infection ◽  
Life Threatening ◽  
Antifungal Immunity ◽  
Epithelial Barriers ◽  
Systemic Infections ◽  
Immune Defences ◽  
The Impact

Abstract Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

scholarly journals Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment

2020 ◽  
Vol 9 (2) ◽  
pp. 297 ◽  
Author(s):  
Annie C. Lajoie ◽  
Anne-Louise Lafontaine ◽  
R. John Kimoff ◽  
Marta Kaminska
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Current Knowledge ◽  
Upper Airway ◽  
Current Evidence ◽  
Obstructive Sleep ◽  
Intermittent Hypoxemia ◽  
And Function ◽  
The Impact ◽  
Sleep Apnea Treatment

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent upper airway obstruction during sleep resulting in intermittent hypoxemia and sleep fragmentation. Research has recently increasingly focused on the impact of OSA on the brain’s structure and function, in particular as this relates to neurodegenerative diseases. This article reviews the links between OSA and neurodegenerative disease, focusing on Parkinson’s disease, including proposed pathogenic mechanisms and current knowledge on the effects of treatment.

scholarly journals Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2369-2379
Author(s):  
Tatyana Pozner ◽  
Martin Regensburger ◽  
Tobias Engelhorn ◽  
Jürgen Winkler ◽  
Beate Winner
Keyword(s):  
Clinical Symptoms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Lower Limbs ◽  
Pathogenic Variants ◽  
Structural Abnormalities ◽  
Neuronal Systems ◽  
And Function ◽  
The Impact

Abstract Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosomal recessive HSP. The majority of SPG11-HSP patients exhibit additional neurological symptoms such as cognitive decline, thin corpus callosum, and peripheral neuropathy. Yet, the mechanisms of SPG11-linked spectrum diseases are largely unknown. Recent findings indicate that spatacsin, the 280 kDa protein encoded by SPG11, may impact the autophagy-lysosomal machinery. In this update, we summarize the current knowledge of SPG11-HSP. In addition to clinical symptoms and differential diagnosis, our work aims to link the different clinical manifestations with the respective structural abnormalities and cellular in vitro phenotypes. Moreover, we describe the impact of localization and function of spatacsin in different neuronal systems. Ultimately, we propose a model in which spatacsin bridges between neurodevelopmental and neurodegenerative phenotypes of SPG11-linked disorders.

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